Induction of apoptosis in mouse brain capillary endothelial cells by cyclosporin A and tacrolimus

Satoko Kochi, Hitomi Takanaga, Hirotami Matsuo, Hisakazu Ohtani, Mikihiko Naito, Takashi Tsuruo, Yasufumi Sawada

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Although cyclosporin A and tacrolimus are used clinically as potent immunosuppressants, there have been reports of neurotoxicity and encephalopathy. A possible mechanism is that these drugs damage the blood- brain barrier (BBB), inducing dysfunction and increased permeability, and are then able to enter the brain. We studied the cytotoxicity of cyclosporin A and tacrolimus, focused on apoptosis induction, using an immortalized cell line established from BALB/c mouse cerebral microvessel endothelial cells (MBEC4). We found that these two drugs induced cell shrinkage, chromatin condensation and DNA fragmentation, which are characteristics of apoptosis. Our data suggest that the induction of apoptosis on the brain capillary endothelial cells may be at least partly involved in the occurrence of immunosuppressant-induced encephalopathy.

Original languageEnglish
Pages (from-to)2255-2260
Number of pages6
JournalLife Sciences
Volume66
Issue number23
Publication statusPublished - 2000 Apr 28
Externally publishedYes

Fingerprint

Endothelial cells
Tacrolimus
Cyclosporine
Brain
Endothelial Cells
Brain Diseases
Immunosuppressive Agents
Apoptosis
DNA Fragmentation
Cytotoxicity
Microvessels
Blood-Brain Barrier
Pharmaceutical Preparations
Chromatin
Condensation
Permeability
Cells
Cell Line
DNA

Keywords

  • Apoptosis
  • Blood-brain barrier
  • Cyclosporin A
  • Encephalopathy
  • Tacrolimus

ASJC Scopus subject areas

  • Pharmacology

Cite this

Kochi, S., Takanaga, H., Matsuo, H., Ohtani, H., Naito, M., Tsuruo, T., & Sawada, Y. (2000). Induction of apoptosis in mouse brain capillary endothelial cells by cyclosporin A and tacrolimus. Life Sciences, 66(23), 2255-2260.

Induction of apoptosis in mouse brain capillary endothelial cells by cyclosporin A and tacrolimus. / Kochi, Satoko; Takanaga, Hitomi; Matsuo, Hirotami; Ohtani, Hisakazu; Naito, Mikihiko; Tsuruo, Takashi; Sawada, Yasufumi.

In: Life Sciences, Vol. 66, No. 23, 28.04.2000, p. 2255-2260.

Research output: Contribution to journalArticle

Kochi, S, Takanaga, H, Matsuo, H, Ohtani, H, Naito, M, Tsuruo, T & Sawada, Y 2000, 'Induction of apoptosis in mouse brain capillary endothelial cells by cyclosporin A and tacrolimus', Life Sciences, vol. 66, no. 23, pp. 2255-2260.
Kochi S, Takanaga H, Matsuo H, Ohtani H, Naito M, Tsuruo T et al. Induction of apoptosis in mouse brain capillary endothelial cells by cyclosporin A and tacrolimus. Life Sciences. 2000 Apr 28;66(23):2255-2260.
Kochi, Satoko ; Takanaga, Hitomi ; Matsuo, Hirotami ; Ohtani, Hisakazu ; Naito, Mikihiko ; Tsuruo, Takashi ; Sawada, Yasufumi. / Induction of apoptosis in mouse brain capillary endothelial cells by cyclosporin A and tacrolimus. In: Life Sciences. 2000 ; Vol. 66, No. 23. pp. 2255-2260.
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